The term "biocompatible" as employed herein means a material that is relatively non-thrombogenic when used in direct contact with blood and is compatible with tissue. Various theories of tissue and blood compatibility of polymeric materials and devices have been advanced over recent years and have resulted in certain controls to the end of making such materials safely implantable into living organisms. Such controls generally can be divided into two categories: (1) materials parameters and (2) structure parameters.
Under the category of materials parameters are hydrophilic/hydrophobic balance, surface energy, chemical nature, and the electrical nature of the surface of materials. Thus, it has been proposed that the higher the water content of the polymer the more closely it will correspond to natural tissue and the greater the level of the biocompatibility. Similarly, it has been proposed that if the surface energy of a synthetic polymer matches that of natural tissue, excellent biocompatibility will result. In the selection of materials, methods have been devised to measure the rate and degree of blood clotting when blood is placed in contact with a synthetic polymeric surface. Also, the presence of an electrical charge is considered to have a substantial effect on its biocompatibility.
The category of structural parameters principally has to do with the mechanical properties, porosity and fiber size of the material. In a vascular prosthesis, compliance is directed to matching the mechanical properties of the host vessel and prosthetic material; whereas, the level of porosity and fiber size selected is concerned more with that which will permit the tissue to ingrow enough to anchor the prosthesis and to promote longterm survival.
A number of problems have been encountered in attaining the desired level of porosity. For instance, arterial prostheses are customarily knits or weaves of DACRON.RTM. or fibrous polytetrafluoroethylene (PTFE). Typically, the porosity of DACRON.RTM. prostheses is on a scale which is visible to the naked eye and results in a preclotting requirement when used surgically for blood conduits. PTFE prostheses are generally made porous by sintering and stretching the PTFE in particle form. Although the porosity of these materials is substantially less than that found in DACRON.RTM. prostheses, it is such that host tissue tends to grow completely through the material and to render it hard, rigid and prone to calcification. Other processes have been devised in an effort to accurately control the porosity of materials. In one process, the voids in a specific type of microporous coral are filled with polymer, and the coral is then dissolved with acid to leave a microporous polymeric structure. In electrostatic spinning processes devised in the past, a polymer in solution is spun into a fiber and laid onto a cylindrical rotating mandrel. The fiber is drawn from the polymer solution by an electric field set up between the mandrel and polymer solution.
Precipitation procedures have been employed in the past, for example, in the formation of thin microporous membranes or filters wherein the pore diameters are of uniform size throughout. Typical procedures for the fabrication of molecular filters are disclosed in U.S. Pat. No. 4,173,689 to Lyman et al, U.S. Pat. No. 3,412,184 to Sharples et al and U.S. Pat. No. 4,203,847 to J. D. Grandine. Thus, U.S. Pat. No. 4,203,847 discloses a process of forming a filter having pores of uniform size and in the range of 250 Angstroms up to 14 micrometers wherein a crystalline polymer solution is applied as a thin film on a traveling belt which is immersed into a precipitation bath that includes a non-solvent for the polymer but which is miscible in the liquid vehicle of the polymer solution. The solution is immersed in the bath until the film has been converted to a porous membrane, after which it is removed from the bath and separated from the belt, any residual solvent being extracted from the membrane and the membrane then dried. Characteristically, the molecular filters in accordance with U.S. Pat. No. 4,203,847 and others are formed out of a crystalline material and are concerned more with the uniformity of pore size in a thin film filter. Similarly, in U.S. Pat. No. 4,173,689, it is said to be necessary to control shrinkage of a membrance by maintaining a uniform pore size throughout. In contrast, applicants' invention is concerned with the biocompatibility of an elastomeric material which is as much as twenty times thicker than filter media and can be reliably and accurately produced by controlled precipitation of a polymer so as to have a selective variation in pore size between its outer and inner skin surfaces with minimal shrinkage. Previous attempts at controlled precipitation of the elastomeric polymers with selective variation in pore size have not been successful, at least in the formation of biocompatible elastomeric materials, principally by reason of the problems associated with controlling the pore size and shrinkage of the material as it is dried.
Polyurethanes and polyurethane ureas in particular are notorious for being difficult to control and reproduce, particularly those utilizing aliphatic diamine chain extenders. In accordance with the present invention, it has been discovered that certain materials selected from the segmented polyetherurethane urea family of polymers, or socalled "spandex" polymers whose chains consist of alternating hard and soft blocks, are suited for use as biocompatible membrane structures when the materials are carefully prepared in solution form with a proper solvent and caused to undergo closely-controlled precipitation, extraction and heat treatment. In particular, it is important that the resultant prostheses have predictably uniform characteristics within close tolerances with respect to tensile strength, elongation and gradation in pore size. The ability to achieve the desired uniformity in characteristics and properties of the prosthesis formed lies in the recognition of those material and structural parameters essential to the formation of a biocompatible structure having the desired characteristics.